Indian Journal of Chemistry Vol. 408, July 200 1 , pp. 622-624

Note

Reductions using LiCIINaBH4: A rapid and efficient cleavage of organic disulfides to

mercaptans t

S Rajaram, K Purushothama Chary & D S Iyengar*

Discovery Laboratory, Organic Division I I Indian Institute of Chemical Technology,

Hyderabad 500 007, India E-mail: iyengar@iict.ap.nic.in Fax: 9 1 -40-7 173387, 7 1 73757

Received 22 November 1 999; accepted (revised) 28 March 2000

A practical and novel reagent system LiCliNaBH4 is used for the reductive cleavage of organic disulfides to mercaptans under mild conditions, in excellent yields.

The universal presence of disulfide and thio moieties in biologically active compounds has led to many new and varied methods for their interconversion ' ,2, Some of the reported methods include sodium hydrogen telluride3, meso-2, 5-dithiol-N, N, N', N'-tetramethyl­adipamide (meso-DTA)4, potassium triisopropoxy borohydride (KIPBH)5, Zn or Sn in the presence of an acid6, Ph3P-dioxane-water7, In-NH4Cl8, However, these methods suffer from drawbacks such as pro­longed reaction period, higher reaction temperature9, and ineffectiveness towards stearically hindered disulfides '0,

Sodium borohydride is considered to be a very mild reducing agent. Methods previously used to modify NaBH4 reactivity include the use of solvent effects and exchange of sodium with other metal cations in the complex hydride" . In continuation of our efforts towards modified borohydride reagents ' 2-2 ' for organic transformations, we observed that a

combination of NaBH4 and LiCI could bring about the efficient conversion of organic disulfides to corre­sponding mercaptans. In this note we report the potential utility of LiCl/NaBH4 reagent system for the reductive cleavage of organic disulfides within 30 min under mild reaction conditions to give high yields of the corresponding mercaptans.

Treatment of one equivalent of an organic disulfide with one equivalent of LiCIINaBH4 reagent system in dry THF under nitrogen at DoC to room temperature provided quantitative formation of the corresponding mercaptans (Scheme I).

When LiCI (1 eq.) reacts with NaBH4 (1 eg.), this generates in situ formation of LiBH4 " . The formation of mercaptans from corresponding organic disulfides is probably due to the in situ formation of LiBH4. The formation of mercaptans from the organic disulfides can be visualized as an initial conjugation of Lithium with the disulfide leading to the formation of the sulfonium ion followed by the hydride delivery (Scheme II).

The generality of the reaction to various disulfides is shown in Table I. Both aliphatic and aromatic including heteroaromatic disulfides are converted smoothly to the mercapto compounds within 30 min. Chemoselective reduction of disulfides is observed in the presence of chloro (entry 4), and nitro (entry 6)

R-S-S-R LiCIINaBl\ .. 2 R-SH

THF, O °C-RT

Scheme l

LiClINaBH .. R �� /R

workup �

�(' H /j-U

-';"':':';::'=-�-I�� 2 R-SH

H

Scheme II

tlICT Communication No: 4407

NOTES

Table I-Reduction of disulfides to mercaptans using LiCIINaBH4

Entry

2

3

4

5

6

7

8

9

1 0

Substrate

el� �el

�s-s �

O�Q,_.o'o'

QH� eH, H,c

H II

(X�)---.-'-<�X)

Product'

(XI NH2

" SH CI�

�SH

I(XCH) SH

H I

CX)-SII �SH

, al l the reactions were completed in 20-30 min. b isolated yields by silica gel column chromatograph� (yields unoptimized) C observed difficulty in isolation due to low b.p. (98 C)

623

Yieldb (%)

95

92

93

89

96

85

80

75

80

60C

624 INDIAN 1 CHEM. SEC. B, JULY 200 I

groups. All the products thus obtained were ful ly characterized by 'H NMR, IR and mass fragmentation analysis.

In conclusion, we have developed an efficient and rapid methodology for the reductive cleavage of a wide range of disulfides to their respecti ve mercap­tans in excellent yields under mild reaction conditions using LiCIINaBH4.

Experimental Section Typical procedure. Into a two-necked round bot­

tom flask equipped with magnetic - bead and nitrogen balloon adaptor was placed LiCI ( 1 eq.) and dry THF (5 mL) syringed i nto it. The contents were cooled to ODC, and NaBH4 (1 eq.) was added in portions. To this reagent system at ODC was added disulfide ( 1 eq .) in dry THF (5 mL) and the contents stirred magnetical ly. After the addition of disulfide, ice cooling was removed and the contents brought to room tempera­ture (35DC). The progress of the reaction monitored by TLC clearly indicated the disappearance of the disulfide in 1 5 min. The contents were cooled and treated with 5% aq. HC\ . The organic layer thus separated was evaporated under vaccum to remove THF. It was extracted with ethyl acetate ( 10 mL), washed with water and dried over anhydrous Na2S04. Evaporation of the organic portion fol lowed by sil ica gel column chromatography provided pure thiol in quantitative yield.

Acknowledgements One of the authors (KPC) thanks the UGC, New

Delhi for the award of research fel lowship.

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